Combined NMR and ab initio analysis of new fluorinated prolines

Fluorinated amino acids hold great potential towards investigating the structure-function relationship of proteins, either by modulating their conformational properties or by introducing the powerful 19F NMR probe. We are interested in synthesizing and using novel fluorinated prolines towards these ends. In a first step, we are performing a very detailed conformational analysis of these compounds, including the trans/cis isomerism and the five-membered ring pucker. However, the accuracy of the current state-of-the-art puckering analysis is limited, mostly (but not solely) due to the accuracy of Karplus relations, which are empirical approximations relating scalar couplings to dihedral angles. To resolve this issue, we are performing an extensive ab initioanalysis for all envisaged fluoroprolines. We aim to develop our own set of relations between ring pucker and scalar couplings that will allow probing the fluoroproline conformation in peptides with NMR spectroscopy with unprecedented accuracy and precision.